Mesalamine

Class: Anti-inflammatory Agents
VA Class: GA900
Chemical Name: 5-Amino-2-hydroxybenzoic acid
Molecular Formula: C₇H₇NO₃
CAS Number: 89-57-6
Brands: Asacol, Canasa, Lialda, Pentasa, Rowasa

Introduction

The 5-amino derivative of salicylic acid; a GI anti-inflammatory agent.^{1 3 4 6 15}

Uses for Mesalamine

Ulcerative Colitis

Used for management of ulcerative colitis (as oral delayed-release tablets or extended-release capsules)^{228 229 231 232 233 236} and to induce (as extended-release capsules and as 1.2-g delayed-release tablets)^{229 236 448} and maintain (as 400-mg delayed-release tablets)^{228 234 235} clinical remission in adults with mildly to moderately active disease.

Management of mildly to moderately active distal ulcerative colitis (as rectal suspension) ^{1 2 3 7 71 72 74 78 93 94 104 154 175 176 177 203 204 205} including ulcerative proctosigmoiditis ^{1 2 7 15 97 99 100 102 120 122 153 154 173 175} and ulcerative proctitis.^{1 2 7 71 72 97 98 122 154}

Management of active ulcerative proctitis (as rectal suppositories).^{217 227 230 237}

Oral preparations of the drug may be preferable to rectal preparations in patients with extensive inflammatory bowel disease, since efficacy of rectal preparations may be limited to disease distal to the splenic flexure.^{86 156}

Crohn’s Disease

Has been used (as extended-release oral preparations) for the management of active Crohn’s disease†^{106 261 339 341 342 343 344 345} and to induce^{300 339 341} and maintain clinical remission^{241 245 248 250 339 348 349 350 351 352 353 354 355 356 357} in adults with mildly to moderately active disease.

Has been used (as rectal preparations) in a limited number of patients for the management of active Crohn’s disease†,⁷⁰ but the role of such therapy in this condition is not as well defined as in the management of ulcerative colitis.^{88 199 200}

Mesalamine Dosage and Administration

Administration

Administer orally^{66 73 80 81 83 85 90 91 96 136 156 164 172 174 228 229 231 233 234 235 236 448} or rectally.^{1 2 7 71 72 74 86 93 94 99 100 102 103 104 105 1 227}

Oral Administration

Administer orally as delayed-release tablets (Asacol, Lialda)^{228 231 233 234 448} or extended-release capsules (Pentasa).^{229 235 236}

Delayed-release tablets should be swallowed whole without breaking the outer coating, since the coating is designed to maintain the integrity of the tablets prior to entering the colon, where the drug is released.^{228 448} Intact or partially intact tablets may be present in stools; if this occurs repeatedly, patients should notify their clinician.²²⁸

1.2-g delayed-release tablets (Lialda): Administer orally with food.⁴⁴⁸

Rectal Administration

Administer rectally as a suspension retention enema^{1 2 7 71 72 74 86 93 94 99 100 102 103 104 105} or suppositories.^{227 230}

Administer rectal suspension preferably at bedtime and retain for about 8 hours.¹ Best results are achieved if the bowel is emptied just prior to enema administration.² Administer according to manufacturer’s instructions.¹

Retain rectal suppositories for ≥1–3 hours, if possible, to achieve maximum benefit.^{70 217 227 230}

Dosage

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Delayed-release tablets have been given in an initial dosage of 20–30 mg/kg daily and then increased up to 60 mg/kg daily.^{333 335}

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets: Usually, 2.4 g daily (given as two 400-mg delayed-release tablets 3 times daily) for 6 weeks.²²⁸

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Usually, 4 g daily in equally divided doses (given as four 250-mg extended-release capsules or two 500-mg extended-release capsules 4 times daily) for up to 8 weeks.²²⁹ Lower dosages (e.g., 2–4 g daily [in divided doses]) have been used†.²⁵⁰

Delayed-release tablets: 2.4 or 4.8 g once daily (given as two or four 1.2-g delayed-release tablets).⁴⁴⁸ Safety and efficacy beyond 8 weeks of treatment have not been established.⁴⁴⁸

Maintenance of Remission

Oral

Delayed-release tablets: Usually, 1.6 g daily (four 400-mg delayed-release tablets) given in divided doses for 6 months.²²⁸ Dosages of 800 mg to 4.8 g daily (in divided doses) also have been used.²⁵⁰

Extended-release capsules: Dosages of 1.5–3 g daily (in divided doses) have been used.²⁵⁰

Advise patients that ulcerative colitis rarely remits completely, and continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.²²⁸

Distal Ulcerative Colitis

Rectal

Suppositories: 1 g (using 1-g suppositories) once daily at bedtime.^{227 230}

Enema suspension: Usually, 4 g once daily (preferably at bedtime).^{1 2 72 78 86 93 94 205}

Although clinical response may be apparent within 3–21 days, therapy with rectal mesalamine usually is continued for 3–6 weeks or until clinical and/or sigmoidoscopic remission is achieved.^{1 227 230}

Efficacy of rectal therapy (in terms of modification of relapse rates) beyond 6 weeks has not been established,^{1 227} but mesalamine has been used rectally for prolonged periods (e.g., >1 year) in some patients.⁹³

Lower dosages^{7 71 99 100 102 104 105 176 203 204 208} or less frequent administration^{93 204} of the rectal drug has been used in some patients†, particularly after initial remission is achieved.

In some patients with distal ulcerative colitis in whom clinical remission occurred following daily administration of 4-g doses of the rectal suspension, dosage was reduced to 4 g every 2 or 3 nights or, occasionally, to less frequent administration.^{93 204} If clinical relapse occurred with such administration, dosage was increased to more frequent use.⁹³ In some patients with distal ulcerative colitis or ulcerative proctosigmoiditis, the rectal suspension also has been used in dosages of 1–3 g daily.^{7 71 99 100 102 104 105 176 203 204 208}

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease†

Oral

Adults have received dosages of 3.2–4.8 g daily (as delayed-release tablets)^{241 243 248 250 339 340 342} or 4 g daily (as extended-release capsules), generally in divided doses.^{300 339} Lower dosages do not appear to be effective.^{106 300 339 367 341}

Prescribing Limits

Pediatric Patients

Ulcerative Colitis† or Crohn’s Disease†

Oral

Maximum 60 mg/kg daily.^{333 335}

Adults

Ulcerative Colitis

Management of Mildly to Moderately Active Ulcerative Colitis

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.^{229 250}

Induction of Remission of Mildly to Moderately Active Ulcerative Colitis

Oral

Extended-release capsules: Maximum 4 g daily in divided doses.²²⁹

Delayed-release tablets (1.2 g; Lialda): Safety and efficacy beyond 8 weeks of therapy not established.⁴⁴⁸

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily, in divided doses.²⁵⁰

Extended-release capsules†: Maximum 3 g daily in divided doses.²⁵⁰

Distal Ulcerative Colitis

Rectal

Enema suspension: Maximum 4 g once daily.^{1 2 72 78 86 93 94 205}

The drug has been used rectally for >1 year.⁹³

Crohn’s Disease†

Management of Mildly to Moderately Active Crohn’s Disease

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses.²⁵⁰

Extended-release capsules: Maximum 4 g daily in divided doses.²⁵⁰

Maintenance of Remission

Oral

Delayed-release tablets (400 mg; Asacol): Maximum 4.8 g daily in divided doses. ²⁵⁰

Extended-release capsules: Maximum 3 g daily in divided doses.²⁵⁰

Special Populations

Geriatric Patients

Careful dosage selection recommended due to possible age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.^{228 230 448}

Cautions for Mesalamine

Contraindications

• 
  

  Extended-release capsules (Pentasa), delayed-release tablets (1.2-g; Lialda), rectal suppositories (Canasa): Known hypersensitivity to salicylates (including aspirin, mesalamine)^{229 230 448} or any ingredient in the respective formulation.^{1 227 228 229 230 448}

  
  

Warnings/Precautions

Sensitivity Reactions

Possible acute intolerance (sensitivity reaction) syndrome (e.g., cramping, abdominal pain, bloody diarrhea, fever, headache, malaise, conjunctivitis, pruritus, rash); may require prompt discontinuance.^{1 2 78 112 114 121 156 180 198 213 227 228 229 230 448} A history of sulfasalazine intolerance, if any, should be reevaluated.^{1 2 198 227 228 230}

Use with caution in patients with a history of hypersensitivity to sulfasalazine.^{1 227 228 230 448}

Sulfite Sensitivity

Rectal suspension contains a sulfite, which may cause allergic-type reactions (including anaphylaxis and life-threatening or less severe asthmatic episodes) in certain susceptible individuals.¹

General Precautions

Renal Impairment

Renal impairment (e.g., minimal change nephropathy, acute and chronic interstitial nephritis, renal failure) and increases in BUN and S_cr reported.^{228 229}

Use with caution and only if the benefits outweigh the risks⁴⁴⁸ in patients with renal impairment.^{1 228 229 230 448}

Renal function should be evaluated prior to initiation of therapy and periodically thereafter.^{1 228 448}

GI Effects

Pancolitis reported rarely in patients receiving rectal mesalamine.^{1 2 227 230}

Possible worsening colitis or symptoms of inflammatory bowel disease (e.g., melena, hematochezia) in patients receiving rectal mesalamine.¹

Potential for prolonged gastric retention of oral delayed-release tablets in patients with pyloric stenosis.^{228 448}

The possibility of acute pancreatitis should be considered in any patient who develops new abdominal complaints while receiving mesalamine therapy.²²⁰

Cardiac Effects

Use with caution in patients with conditions predisposing them to the development of myocarditis or pericarditis.⁴⁴⁸ The possibility of pericarditis should be considered in any patient who develops chest pain or dyspnea during mesalamine therapy.¹ Discontinuance may be needed.²²⁷

Specific Populations

Pregnancy

Category B.^{1 228 229 230 448}

Lactation

Distributed into milk following oral administration.^{228 229} Use with caution.^{228 229 448}

Not known whether the rectal drug is distributed into milk.^{1 227 230} Use of rectal mesalamine usually not recommended,^{1 227} although one manufacturer of rectal suppositories states the preparation may be used with caution.²³⁰

Pediatric Use

Safety and efficacy not established in children.^{1 228 229 230 448}

Has been used (as oral delayed-release tablets) for the management of inflammatory bowel disease (i.e., mild ileal, ileocecal, ileocolonic, or colonic disease) and (as rectal mesalamine suspension) in those with left-sided colitis in a limited number of pediatric patients†.^{59 199 200 333 335} (See Pediatric Patients under Dosage.)

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger patients.^{228 230 448} Response does not appear to differ from that in younger adults; however, drug dosage should be selected cautiously.^{230 448}

Possibility of increased incidence of blood dyscrasias (i.e., agranulocytosis, neutropenia, pancytopenia); CBCs should be monitored closely.²²⁸

Because mesalamine is substantially eliminated by kidneys, assess renal function prior to initiation of therapy and periodically thereafter since geriatric patients more likely to have decreased renal function.²²⁸

Hepatic Impairment

Use with caution in patients with hepatic impairment.^{229 448}

Renal Impairment

Use with caution in patients with renal impairment.^{1 228 229 230}

Common Adverse Effects

Oral therapy: Headache, rash, vomiting, diarrhea, flatulence, constipation, nausea, dyspepsia, abdominal pain, fever, arthralgia, flu syndrome.^{228 229 448}

Rectal therapy: Headache, abdominal pain, nausea, diarrhea, gas/flatulence, fever, dizziness, rectal pain, rash, leg/joint pain, flu syndrome.^{1 227 230}

Interactions for Mesalamine

No known drug interactions.^{228 229}

Specific Drugs

Drug	Interaction
Azathioprine	Possible increased risk of hematologic toxicity448
Digoxin	Decreased GI absorption of digoxin with concomitant sulfasalazine or aminosalicylic acid;115 143 195 not known whether mesalamine alters digoxin absorption199 200
Mercaptopurine	Possible increased risk of hematologic toxicity448
Nephrotoxic drugs (e.g., NSAIAs)	Possible increased nephrotoxicity448

Mesalamine Pharmacokinetics

Absorption

Bioavailability

Following oral administration of the 400-mg delayed-release tablets (Asacol), approximately 28% of mesalamine is absorbed and the remainder of the dose is available for topical activity and fecal excretion.²²⁸

Following oral administration of extended-release capsules (Pentasa), about 20–30% of the drug is absorbed.²²⁹

Following oral administration of the 1.2-g delayed-release tablets (Lialda), about 21–22% of the drug is absorbed.⁴⁴⁸

Rectally administered suspension is poorly absorbed from the GI tract (about 15% [range: 5–35%]).^{1 2 15 43 47 49 65 68 210 227} The rectal suspension usually is retained for about 3.5–12 hours after administration as an enema;^{1 2 42 47} prolonged retention may increase absorption of the drug.^{199 200}

Variably absorbed following rectal administration of the suppositories.²³⁰ Rectal suppositories usually are retained for 1–3 hours after administration.²²⁷

Food

Food does not appear to affect absorption of the 400-mg delayed-release tablets (Asacol).²²⁸

Food decreases rate of absorption and increases extent of absorption of the 1.2-g delayed-release tablets (Lialda).⁴⁴⁸

Distribution

Extent

Following oral or IV (IV preparation currently not available in the US) administration, the drug may be distributed into kidneys.^{1 199}

Rectal suspension distributes from the rectum into the colon, generally reaching the splenic flexure^{7 42 95 207} and possibly the ascending colon.²⁰⁷ Rectal suppositories distribute to some extent in rectal tissues.²³⁰

Oral mesalamine crosses the placenta;^{3 47 108 229 448} serum concentrations of mesalamine in umbilical cord and amniotic fluid are very low.¹⁰⁸

Not known whether rectal mesalamine crosses the placenta.³

Oral mesalamine is distributed into milk.^{228 229}

Not known whether rectal mesalamine is distributed into milk.^{1 2 6}

Plasma Protein Binding

Approximately 44–55% (as unchanged drug).^{3 54 60}

Approximately 43% at a concentration of 2.5 mcg/mL.⁴⁴⁸

Elimination

Metabolism

Rapidly metabolized, principally in the liver to form N-acetyl-5-aminosalicylic acid.^{3 47 63 70 228 448}

Elimination Route

Following oral administration, excreted in urine (about 20%) mainly as metabolites^{46 228 229} and in feces.²²⁹

Following rectal administration, principally excreted in feces (about 50%),^{47 71} as unchanged drug and metabolites,^{1 6} and in urine^{1 2 3 6 42} (about 10–35%).^{1 2 3 6 42 68 71}

Half-life

400-mg delayed-release tablets (Asacol): 12 hours (range: 2–15 hours).²²⁸

1.2-g delayed-release tablets (Lialda): 7–9 hours (for mesalamine) and 8–12 hours (for N-acetyl-5-aminosalicylic acid metabolite).⁴⁴⁸

Rectal suspension: 0.5–1.5 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).^{1 3 47 56 60 63}

Rectal suppositories: 0.5–7 hours (for mesalamine) and 5–10 hours (for N-acetyl-5-aminosalicylic acid metabolite).^{227 230}

Stability

Storage

Oral

Extended-release Capsules

25°C (may be exposed to 15–30°C).²²⁹

Delayed-release Tablets

400-mg tablets: 20–25°C.²²⁸

1.2-g tablets: 15–25°C (may be exposed to 30°C).⁴⁴⁸

Rectal

Suppositories

<25°C.²³⁰ Do not freeze; keep out of reach of children.²³⁰

Suspension

20–25°C (may be exposed to 15–30°C); keep out of reach of children.^{1 6} May darken with time once the container has been removed from the foil wrap;¹ dark brown suspensions should be discarded.^{1 199}

ActionsActions

• 
  

  Exerts local (rather than systemic)^{1 2 3 5 7 42 47 49 65 68 69 70 95 156 173 228 229 230 448} anti-inflammatory effects in the GI tract.^{1 2 3 4 5 7 9 10 13 26 76 168 183}

  
  


• 
  

  May reduce inflammation in the colon by inhibiting cyclooxygenase and lipoxygenase,^{1 2 3 10 12 13 14 168 228 229} which catalyze the formation of prostaglandin precursors (endoperoxides) and of leukotrienes^{1 2 3 5 9 10 12 13 26 39 76 168 183 210} and hydroxyeicosatetraenoic acids, respectively, from arachidonic acid and/or its metabolites.^{5 10 13 210}

  
  

Advice to Patients

• 
  

  Importance of swallowing delayed-release tablets whole without breaking the outer coating.^{228 448}

  
  


• 
  

  Importance of taking 1.2-g delayed-release tablets with food.⁴⁴⁸

  
  


• 
  

  Importance of informing patients that intact or partially intact tablets may be present in stools and if this occurs repeatedly, they should notify their clinician.²²⁸

  
  


• 
  

  Importance of informing patients that the rectal suspension and suppositories will cause staining of direct contact surfaces, including, but not limited to, fabrics, flooring, painted surfaces, marble, granite, vinyl, and enamel¹ and therefore, they should carefully choose a suitable location for administration of the rectal suspension.^{1 230}

  
  


• 
  

  Importance of informing patients with sulfasalazine sensitivity^{1 2 78 87 121 180 228 230} to discontinue mesalamine therapy and contact their clinician if signs of sensitivity (e.g., rash, fever) develop^{1 2 198 230} or increased diarrhea or rectal bleeding occurs.²⁰⁰

  
  


• 
  

  Importance of informing clinicians of existing pancreatitis.²³⁰

  
  


• 
  

  Importance informing patients that ulcerative colitis rarely remits completely and that continued use of maintenance dosages of mesalamine may substantially decrease the risk of relapse.²²⁸

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

  
  


• 
  

  Importance of informing patients of other important precautionary information. (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Mesalamine

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Oral	Capsules, extended-release	250 mg	Pentasa	Shire
		500 mg	Pentasa	Shire
	Tablets, delayed-release	400 mg	Asacol	Procter & Gamble
		1.2 g	Lialda	Shire
Rectal	Suppositories	1 g	Canasa	Axcan
	Suspension	4 g/60 mL	Mesalamine Suspension Enema
			Rowasa Suspension Enema	Alaven

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Apriso 0.375GM 24-hr Capsules (SALIX PHARMACEUTICALS INC.): 120/$271.38 or 360/$781.93

Asacol 400MG Enteric-coated Tablets (WARNER CHILCOTT PHARMA): 30/$70.6 or 90/$180.72

Asacol HD 800MG Enteric-coated Tablets (WARNER CHILCOTT PHARMA): 90/$338.85 or 180/$656.48

Canasa 1000MG Suppositories (AXCAN PHARMA US): 30/$488.34 or 90/$1437.86

Lialda 1.2GM Enteric-coated Tablets (SHIRE US INC.): 120/$725.99 or 360/$2089.94

Mesalamine 4GM Enema (TEVA PHARMACEUTICALS USA): 60/$35.99 or 120/$59.98

Pentasa 250MG Controlled-release Capsules (SHIRE US INC.): 240/$290.98 or 720/$835.97

Pentasa 500MG Controlled-release Capsules (SHIRE US INC.): 30/$82.07 or 90/$222.45

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2009. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† Use is not currently included in the labeling approved by the US Food and Drug Administration.

References

1. Alaven Pharmaceutical LLC. Rowasa (mesalamine) rectal suspension enema prescribing information. Marietta, GA; 2008 Aug.

2. Reid-Rowell. Rowasa (mesalamine): a product profile. Marietta, GA; 1988 Mar.

3. Bondesen S, Rasmussen SN, Rask-Madsen J et al. 5-Aminosalicylic acid in the treatment of inflammatory bowel disease. Acta Med Scand. 1987; 221:227-42. [IDIS 232774] [PubMed 3296672]

4. Weintraub M, Evans P. 5-Aminosalicylic acid: an old, ″new″ treatment for inflammatory bowel disease. Hosp Formul. 1987; 22:528-33.

5. Peppercorn MA. Sulfasalazine and related new drugs. J Clin Pharmacol. 1987; 260-5. (IDIS 228622)

6. Reid-Rowell. Rowasa (mesalamine) product information form for the American Hospital Formulary Service. Marietta, GA; 1988 Apr.

7. Anon. Mesalamine for ulcerative colitis. Med Lett Drugs Ther. 1988; 30:53-6. [PubMed 3283508]

8. Allgayer H, Sonnenbichler J, Kruis W et al. Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites. Arzneimittelforschung. 1985; 35:1457-9. [PubMed 2867770]

9. Ligumsky M, Karmeli F, Sharon P et al. Enhanced thromboxane A₂ and prostacyclin production by cultured rectal mucosa in ulcerative colitis and its inhibition by steroids and sulfasalazine. Gastroenterology. 1981; 81:444-9. [IDIS 139848] [PubMed 6114012]

10. Sharon P, Ligumsky M, Rachmilewitz D et al. Role of prostaglandins in ulcerative colitis. Gastroenterology. 1978; 75:638-40. [PubMed 30669]

11. Azad Khan AK, Piris J, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet. 1977; 2:892-5. [IDIS 76335] [PubMed 72239]

12. Lauritsen K, Laursen LS, Bukhave K et al. Effects of topical 5-aminosalicylic acid and prednisolone on prostaglandin E₂ and leukotriene B₄ levels determined by equilibrium in vivo dialysis of rectum in relapsing ulcerative colitis. Gastroenterology. 1986; 91:837-44. [IDIS 221448] [PubMed 3017804]

13. Donowitz M. Arachidonic acid metabolites and their role in inflammatory bowel disease: update requiring addition of a pathway. Gastroenterology. 1985; 88:580-7. [IDIS 196055] [PubMed 2856909]

14. Isselbacher KJ. The role of arachidonic acid metabolites in gastrointestinal homeostasis: biochemical, histological and clinical gastrointestinal effects. Drugs. 1987; 33(Suppl 1):38-46. [IDIS 230964] [PubMed 2885170]

15. Lewis JH. Summary of the 31st meeting of the Food and Drug Administration Gastrointestinal Drugs Advisory Committee December 8-9, 1986. Am J Gastroenterol. 1987; 82:443-7.

16. Sharon P, Stenson WF. Metabolism of arachidonic acid in acetic acid colitis in rats. Gastroenterology. 1985; 88:55-63. [PubMed 3917261]

17. Dull BJ, Salata K, van Langenhove A et al. 5-Aminosalicylate: oxidation by activated leukocytes and protection of cultured cells from oxidative damage. Biochem Pharmacol. 1987; 36:2467-72. [PubMed 3038125]

18. Molin L, Stendahl O. The effect of sulfasalazine and its active components on human polymorphonuclear leukocyte function in relation to ulcerative colitis. Acta Med Scand. 1979; 206:451-7. [IDIS 108764] [PubMed 43662]

19. Hillier K, Mason PI, Pacheco S et al. Ulcerative colitis: effect of sulphasalazine, its metabolites and indomethacin on the ability of human colonic mucosa to metabolize prostaglandins in vitro. Br J Pharmacol. 1982; 76:157-61. [IDIS 150404] [PubMed 6123357]

20. Rhodes JM, Jewell DP. Inhibition of leucocyte motility by drugs used in inflammatory bowel disease. Gut. 1980; 21:A452-3. [PubMed 6450718]

21. Hoult JRS, Page H. 5-Aminosalicylic acid, a co-factor for colonic prostacyclin synthesis? Lancet. 1981; 2:255. Letter. (IDIS 136287)

22. Holdstock G, Chastenay BF, Krawitt EL. Increased prostaglandin producing suppressor cells in inflammatory bowel disease not sensitive to sulfasalazine. Gastroenterology. 1981; 80:1177.

23. Das K, Zapp B, Rubinstein A. In vivo and in vitro effect of sulfasalazine on lymphocyte in inflammatory bowel disease (IBD): systemic immunological parameters in idiopathic proctitis (IP). Gastroenterology. 1976; 70:A17.

24. Smith PR, Dawson DJ, Swan CHJ. Prostaglandins and sulphasalazine. Lancet. 1978; 2:260.

25. Sharon P, Stenson WF. Enhanced synthesis of leukotriene B₄ by colonic mucosa in inflammatory bowel disease. Gastroenterology. 1984; 86:453-60. [PubMed 6319219]

26. Kirsner JB, Shorter RG. Recent developments in ″nonspecific″ inflammatory bowel disease: first of two parts. N Engl J Med. 1982; 306:775-85. [IDIS 146719] [PubMed 7038488]

27. Anon. Sulphasalazine:

Intal CFC-free Inhaler

Intal CFC-Free Inhaler
5mg
Pressurised inhalation, suspension

sodium cromoglicate

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• This medicine has been prescribed for you.
  
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In this leaflet:

• 1. What Intal is and what it is used for


• 2. Before you use Intal


• 3. How to use Intal


• 4. Possible side effects


• 5. How to store Intal


• 6. Further information

What Intal is and what it is used for

Intal CFC-free Inhaler (called Intal in this leaflet) contains a medicine called sodium cromoglicate. This belongs to a group of medicines called anti-allergics.

It works by having an effect deep in the air passages of your lungs. It also lowers your response when you are exposed to substances to which you are allergic.

Intal is used to help prevent asthma attacks and may be called a ‘preventer’:

• Intal will not help an asthma attack that has already started


• You will need to use a different inhaler, called a ‘reliever’, for these attacks (see Using a ‘reliever’ inhaler in Section 3)

Before you use Intal

Do not use this medicine and tell your doctor if:

• You are allergic (hypersensitive) to sodium cromoglicate or any of the other ingredients of Intal (listed in Section 6: Further information).

Signs of an allergic reaction include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue

Do not use this medicine if the above applies to you. If you are not sure, talk to your
doctor or pharmacist before using Intal.

Take special care with Intal:

Check with your doctor or pharmacist before using your medicine if

• You have recently stopped taking ‘steroids’ and your asthma is getting worse (see Taking other medicines below)


• You are suffering from stress, trauma, infections or other illnesses

If you are not sure if any of the above apply to you, talk to your doctor or pharmacist before using Intal.

Taking other medicines

Please tell your doctor or pharmacist if you are taking or have recently taken any other medicines. This includes medicines you buy without a prescription, including herbal medicines. This is because Intal can affect the way some other medicines work. Also some medicines can affect the way Intal works.

In particular, tell your doctor if you are also using a steroid medicine:

• This can be either an inhaler (such as beclometasone) or a tablet (such as prednisolone)


• If you are using a steroid as well as Intal, your doctor may decide to lower the amount of steroid taken or gradually stop the steroid altogether

If your steroid treatment has been reduced or stopped and your asthma then gets worse you must tell your doctor straight away. They may wish to increase or re-start the steroid treatment.

Pregnancy and breast-feeding

Talk to your doctor before using this medicine if you are pregnant, might become pregnant or think you may be pregnant.

If you are breast-feeding or planning to breast-feed, talk to your doctor or pharmacist before using this medicine.

How to use Intal

Always use Intal exactly as your doctor has told you. You should check with your doctor or pharmacist if you are not sure.

Using this medicine

• It is important to use this medicine every day, even if you have no signs of asthma


• This medicine is taken by breathing in through your mouth (see ‘How to use your inhaler’ below)


• You may need to use Intal for several weeks for it to work best


• Your asthma may get worse if you have an infection, are unwell or come into contact with anything to which you are allergic. If this happens, talk to a doctor straight away


• If you feel the effect of your medicine is too weak or too strong, do not change the dose yourself, but ask your doctor, especially if you think it is too weak

How much to use (adults, elderly and children)

• The starting dose is two puffs (inhalations) four times each day


• Taking puffs at meal times and at bedtime may help you to remember to use it


• When your asthma gets better, your doctor may suggest that you lower your daily dose to one puff four times each day


• Your doctor may also suggest you take an additional dose before exercise


• Sometimes when your asthma is bad or when you come into contact with anything to which you are allergic, your doctor may change how much you use. Your dose may be increased to two puffs six to eight times each day

Using a ‘reliever’ inhaler

• If your doctor has advised you to use a ‘reliever’ inhaler at the same time as Intal, it is best to use your ‘reliever’ inhaler before using your Intal Inhaler. This will open the airways and allow the Intal to get down into them better



• Keep your ‘reliever’ inhaler at all times in case of a sudden attack or if your asthma gets worse. Talk to your doctor if it takes more puffs than usual from your ‘reliever’ inhaler to control your symptoms

How to use your Intal Inhaler (An adult should help small children use their inhaler properly)

• 1. Open

Remove the mouthpiece cover and check that the mouthpiece is clean.

• 2. Shake

Shake the inhaler well (at least 5 times).

• If you are using this inhaler for the first time, release 4 puffs into the air


• If the inhaler has not been used for more than 3 days, release 1 or 2 puffs into the air

• 3. Inhale

• Hold the inhaler upright with your thumb on the base


• Hold the inhaler well away from your mouth


• Breathe out as far as is comfortable


• DO NOT breathe out through the inhaler. This is to stop moisture from collecting and blocking the spray

• Put the mouthpiece in your mouth and close your lips tightly around it


• Start to breathe in slowly and deeply through your mouth then….


• Immediately press the metal canister down firmly to release a puff of medicine,
  while keeping breathing in slowly and deeply

• 4. Hold

• Remove the inhaler from your mouth and hold your breath for about 10 seconds or as long as is comfortable



• Breathe out slowly

• 5. Repeat

If your doctor has told you to take 2 puffs each time you use your inhaler:

• Wait for one minute after the first puff. Then repeat steps 3 to 4 once more

• 6. Close

After use, always replace the mouthpiece cover to keep out dust and fluff.

Important things to make sure you are using the inhaler properly

• Practice in front of a mirror or with a nurse, pharmacist or doctor from time to time. If you see a mist escaping from your mouth or around the sides of the canister you need to try to use your inhaler better:
  
  
  • Be sure to have your lips closed properly around the mouthpiece
  
  
  • Be sure to start breathing in before pressing the canister
  
  



• Adults should supervise the use of Intal in small children.

If you or a child use more Intal than you should

If you or a child uses more Intal than you should, talk to a doctor as soon as possible.

If you forget to use Intal

If you forget a dose, take it as soon as you remember it. However, if it is nearly time for the next dose, skip the missed dose. Do not take a double dose to make up for a forgotten dose.

If you stop using Intal

Keep using Intal until your doctor tells you to stop. Do not stop using Intal just because you feel better. If you stop, your illness may get worse.

When your doctor says that you can stop using Intal, your dose will be lowered gradually over a week.

How to clean

It is very important to keep the plastic body of the inhaler clean. This helps to stop the build-up of powder. Clean the plastic body at least twice a week. No harm will come from washing the plastic body and mouthpiece cover every day.

• 1. Remove

• Remove the metal canister and put it in a safe place


• Take off the mouthpiece cover

• 2. Wash

• Wash the plastic body of the inhaler thoroughly in hand hot water from both ends

• Wash through the top for a minute


• Wash through the bottom for a minute


• Then wash the mouthpiece cover

• 3. Dry

• Shake off any water that is left and leave to dry in a clean warm place overnight


• When completely dry, put the metal canister back into the plastic body of the inhaler. Then replace the mouthpiece cover


• If the metal canister will not slide easily into the plastic mouthpiece, press the white rubber cover firmly back down onto the metal canister


• Use the second Intal Inhaler you have been given while the other inhaler is drying

If the inhaler becomes blocked

• Soak the plastic mouthpiece in hand hot water for 20 minutes before you wash it under the tap from both ends (as above)


• Never try to unblock the inhaler with a pin, as this will damage the inhaler

Do not put the metal canister into water

Do not remove the rubber cover from the metal canister

If you have any further questions on the use of this product, ask your doctor or pharmacist.

Possible side effects

Like all medicines, Intal can cause side effects, although not everybody gets them.

Stop using Intal and see a doctor or go to a hospital straight away if:

• You have an allergic reaction to Intal. The signs may include: a rash, swallowing or breathing problems, swelling of your lips, face, throat or tongue



• You have a bad attack of wheezing, difficulty breathing or tightness in the
  chest (something called bronchospasm). People who are allergic to Intal can also experience these side effects. If this happens, do not use your Intal Inhaler. Use your ‘reliever’ inhaler instead and contact a doctor straight away. The doctor may decide to stop your treatment with Intal



• Lung problems including inflammation of the lungs. This means you may have a lung infection called ‘eosinophilic pneumonia’.
  
  
  Signs include:



• feeling unwell or less hungry, a high temperature (fever) lasting 2 to 3 days


• difficulty breathing, shortness of breath and cough.

Talk to your doctor or pharmacist if any of the side effects gets serious or lasts longer than a few days, or if you notice any side effects not listed in this leaflet:

• Sore throat - drinking water after you use your inhaler may help this


• Coughing


• Headache


• Sneezing, runny or blocked nose

How to store Intal

Keep this medicine in a safe place where children cannot see or reach it.

Do not use Intal Inhaler after the expiry date which is stated on the label and carton. The expiry date refers to the last day of that month.

Do not refrigerate or freeze. The aerosol inhaler canister is pressurised. Protect the aerosol from heat or direct sunlight, do not puncture or incinerate even when it is empty.

Medicines should not be disposed of via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures will help to protect the environment.

Further Information

What Intal Inhaler contains

• The active substance is sodium cromoglicate. Each puff (inhalation) contains 5mg of sodium cromoglicate


• The other ingredients are polyvidone K30, polyethylene glycol (PEG) 600, apaflurane HFA 227 - a non ozone depleting propellant


• This product contains no chlorofluorocarbons

What Intal Inhaler looks like and contents of the pack

• Intal is a metered dose inhaler supplied in an aluminium can fitted with a metering valve which delivers 112 actuations. Each actuation contains 5 mg of sodium cromoglicate.


• Each can of Intal comes with a plastic adaptor (inhaler) with a dust-cap

Marketing Authorisation Holder and Manufacturer

Marketing Authorisation Holder

Sanofi-aventis

One Onslow Street

Guildford

Surrey

GU1 4YS

UK

Tel:01483 505515

Fax:01483 535432

email:uk-medicalinformation@sanofi-aventis.com

Manufacturer

Aventis Pharma Ltd

Holmes Chapel

Cheshire

CW4 8BE

UK

This leaflet does not contain all the information about your medicine. If you have any questions or are not sure about
anything, ask your doctor or pharmacist.

This leaflet was last revised in May 2007

© Sanofi-aventis, 2001 – 2007

Non-Drowsy Sudafed Decongestant Nasal Spray

1. Name Of The Medicinal Product

Non-Drowsy Sudafed Decongestant Nasal Spray

Sudafed Blocked Nose Spray

2. Qualitative And Quantitative Composition

Non-Drowsy Sudafed Decongestant Nasal Spray is an aqueous solution of Xylometazoline Hydrochloride 0.1% w/v presented in a metered-dose pack, delivering 0.14 ml per actuation.

For excipients see 6.1.

3. Pharmaceutical Form

Aqueous solution

4. Clinical Particulars

4.1 Therapeutic Indications

Non-Drowsy Sudafed Decongestant Nasal Spray is indicated for the symptomatic relief of nasal congestion associated with the common cold, influenza, sinusitis, allergic and non-allergic rhinitis, and other upper respiratory tract allergies.

4.2 Posology And Method Of Administration

Adults and children 12 years and over:

Nasal. One spray to be expressed into each nostril 2-3 times daily, as necessary.

Maximum daily dose: 3 sprays.

Use for more than seven consecutive days is not recommended, [See Undesirable effects].

Children under 12 years:

Non-Drowsy Sudafed Decongestant Nasal Spray is not recommended for children under 12 years of age.

The Elderly

Experience has indicated that normal adult dosage is appropriate, [See Pharmacokinetics in the elderly].

Hepatic/renal dysfunction

Normal adult dosage is appropriate, [See Pharmacokinetic properties].

4.3 Contraindications

Non-Drowsy Sudafed Decongestant Nasal Spray is contraindicated in individuals with known hypersensitivity to the product or any of its constituents.

Non-Drowsy Sudafed Decongestant Nasal Spray is contraindicated in individuals who are taking or have taken, monoamine oxidase inhibitors within the preceding two weeks.

Non-Drowsy Sudafed Decongestant Nasal Spray is contraindicated in individuals with hypophysectomy or surgery exposing dura mater.

4.4 Special Warnings And Precautions For Use

There is minimal systemic absorption with topically applied imidazoline sympathomimetics such as xylometazoline, however, Non-Drowsy Sudafed Decongestant Nasal Spray should be used with caution in patients suffering coronary artery disease, hypertension, hyperthyroidism or diabetes mellitus.

4.5 Interaction With Other Medicinal Products And Other Forms Of Interaction

Due to the low systemic absorption of xylometazoline when administered intra-nasally, interaction with drugs administered via other routes is considered unlikely.

4.6 Pregnancy And Lactation

No foetal toxicity or fertility studies have been carried out in animals. In view of its potential vasoconstrictor effect, it is advisable to take the precaution of not using Non-Drowsy Sudafed Decongestant Nasal Spray during pregnancy.

4.7 Effects On Ability To Drive And Use Machines

No special comment - unlikely to produce an effect.

4.8 Undesirable Effects

Xylometazoline nasal preparations are generally well tolerated following short-term use and local side effects are mild and infrequent. Localised burning, stinging, itching, soreness, dryness or irritation and sneezing may occur occasionally. Rarely, nausea and headache may occur.

Rebound congestion has been reported occasionally, particularly following longer-term use of xylometazoline.

4.9 Overdose

Symptoms and signs

Systemic action is unlikely when applied nasally due to the local vasoconstriction that inhibits absorption. If systemic absorption does occur xylometazoline as an α₂-adrenergic agonist could be expected to produce effects similar to those of clonidine with a short lived rise in blood pressure, followed by more prolonged hypotension and sedation.

Treatment

Treatment of overdose should be supportive.

5. Pharmacological Properties

5.1 Pharmacodynamic Properties

Xylometazoline is a sympathomimetic amine of the imidazoline class.

It act directly on α-adrenoreceptors but does not act on ß

5.2 Pharmacokinetic Properties

Absorption, Distribution, Metabolism and Elimination

Little information is available concerning the absorption, distribution, metabolism and elimination of xylometazoline in man. Absorption into the nasal mucosal tissues is rapid.

Pharmacokinetics in Renal/Hepatic Impairment

There have been no specific studies of Non-Drowsy Sudafed Decongestant Nasal Spray or xylometazoline in hepatic or renal impairment.

Pharmacokinetics in the Elderly

There have been no specific clinical studies of Non-Drowsy Sudafed Decongestant Nasal Spray or xylometazoline in the elderly.

5.3 Preclinical Safety Data

Mutagenicity

There is insufficient information available to determine whether xylometazoline has mutagenic potential.

Carcinogenicity

There is insufficient information available to determine whether xylometazoline has carcinogenic potential.

Teratogenicity

There is insufficient information available to determine whether xylometazoline has teratogenic potential.

Fertility

No studies have been conducted in animals to determine whether xylometazoline has the potential to impair fertility. There is no information on the effects of Non-Drowsy Sudafed Decongestant Nasal Spray on fertility.

6. Pharmaceutical Particulars

6.1 List Of Excipients

Benzalkonium chloride solution

Disodium edetate

Sodium dihydrogen phosphate dihydrate

Sodium monohydrogen phosphate dihydrate

Sodium chloride

Sorbitol solution, 70% (Non crystalline)

Purified water

6.2 Incompatibilities

None known

6.3 Shelf Life

3 years.

6.4 Special Precautions For Storage

Do not store above 25°C.

6.5 Nature And Contents Of Container

Amber glass bottle of either 10 ml or 15 ml nominal fill volume.

The bottle is sealed with an integral snap-on metered 0.14 ml pump consisting of a white plastic actuator and natural polyethylene pull-off overcap.

6.6 Special Precautions For Disposal And Other Handling

None applicable.

7. Marketing Authorisation Holder

McNeil Products Limited

Foundation Park

Roxborough Way

Maidenhead

Berkshire SL6 3UG

United Kingdom.

8. Marketing Authorisation Number(S)

PL 15513/0074

9. Date Of First Authorisation/Renewal Of The Authorisation

21/04/99

10. Date Of Revision Of The Text

13 January 2010

Embeda Extended-Release Capsules

Pronunciation: MORE-feen/nal-TREX-ohn
Generic Name: Morphine/Naltrexone
Brand Name: Embeda

Embeda Extended-Release Capsules are a narcotic pain reliever used for around-the-clock treatment of moderate or severe pain. It should not be used to treat occasional pain.

Embeda Extended-Release Capsules should only be used by patients who have already been taking narcotic pain medicine and are tolerant to its effect. The use of Embeda Extended-Release Capsules by people who are not used to taking narcotic pain medicine may cause severe and sometimes fatal breathing problems.

Swallow Embeda Extended-Release Capsules whole. Do NOT crush, chew, or dissolve Embeda Extended-Release Capsules; it may cause the release of too much medicine into the bloodstream, which could be fatal. Doing this may also release the naltrexone in Embeda Extended-Release Capsules, which may cause withdrawal symptoms.

If you have trouble swallowing Embeda Extended-Release Capsules whole, you may sprinkle the contents of the capsule on a small amount of applesauce and then swallow the mixture. Do NOT chew, crush, or dissolve the contents of the capsule before swallowing.

Do not drink alcoholic beverages or take any prescription or nonprescription medicines that contain alcohol at any time while you are taking Embeda Extended-Release Capsules. Doing this may cause too much medicine to be absorbed too quickly and may cause severe or possibly fatal side effects.

Embeda Extended-Release Capsules are used for:

Managing moderate to severe pain that continues around-the-clock and is expected to last for a long period of time. Embeda Extended-Release Capsules are used in patients who have already been taking narcotic pain medicine and are tolerant to its effects.

Embeda Extended-Release Capsules are a narcotic pain reliever. It works in the brain to dull pain. Embeda Extended-Release Capsules also contains naltrexone, an opioid receptor antagonist, inside a special coating. If Embeda Extended-Release Capsules are crushed or chewed, the naltrexone will be released and may cause withdrawal symptoms.

Do NOT use Embeda Extended-Release Capsules if:

• you are allergic to any ingredient in Embeda Extended-Release Capsules


• you have paralysis of the stomach or intestines


• you have very slow or shallow breathing, severe asthma, hypercapnia (high levels of carbon dioxide in your blood), or you are having an asthma attack


• you are taking sodium oxybate (GHB)


• you are taking or have taken a monoamine oxidase inhibitor (MAOI) (eg, phenelzine) within the past 14 days

Contact your doctor or health care provider right away if any of these apply to you.

Before using Embeda Extended-Release Capsules:

Some medical conditions may interact with Embeda Extended-Release Capsules. Tell your doctor or pharmacist if you have any medical conditions, especially if any of the following apply to you:

• if you are pregnant, planning to become pregnant, or are breast-feeding


• if you are taking any prescription or nonprescription medicine, herbal preparation, or dietary supplement


• if you have allergies to medicines, foods, or other substances


• if you are allergic to other narcotic pain medicines (eg, codeine)


• if you have diarrhea or constipation, are dehydrated, have low blood volume, or are in shock


• if you have severe drowsiness or are very weak, very overweight, or in very poor health


• if you have increased pressure in the head, a recent head injury, or an abnormal growth in the brain


• if you have gallbladder problems, pancreas problems (eg, inflammation), bladder blockage or trouble urinating, enlarged prostate, stomach or bowel problems (eg, blockage, inflammation, severe diarrhea caused by antibiotic use), or have had recent stomach or bowel surgery


• if you have a history of liver or kidney problems, heart problems (eg, cor pulmonale), low blood pressure, lung or breathing problems (eg, asthma, chronic obstructive pulmonary disease [COPD]), sleep apnea (trouble breathing when you sleep), thyroid problems (eg, underactive thyroid), adrenal gland problems (eg, Addison disease), or curvature of the spine (eg, scoliosis)


• if you have a history of seizures, mental or mood problems (eg, hallucinations), suicidal thoughts or actions, alcohol or other substance abuse or dependence, or if you are currently experiencing alcohol withdrawal


• if you are taking another medicine that contains naltrexone


• if you will be having surgery, or if you have a gastric or nasogastric tube

Some MEDICINES MAY INTERACT with Embeda Extended-Release Capsules. Tell your health care provider if you are taking any other medicines, especially any of the following:

• Cimetidine, MAOIs (eg, phenelzine ), muscle relaxants (eg, cyclobenzaprine), other narcotic pain medicines (eg, oxycodone), phenothiazines (eg, chlorpromazine), or quinidine because the risk of severe side effects (eg, severe drowsiness, very slow or shallow breathing, confusion, seizures) may be increased


• Anticholinergics (eg, scopolamine) because the risk of trouble urinating and severe constipation may be increased


• Narcotic agonists/antagonists (eg, pentazocine) or rifampin because they may decrease Embeda Extended-Release Capsules's effectiveness


• Sodium oxybate (GHB) because the risk of its side effects may be increased by Embeda Extended-Release Capsules


• Diuretics (eg, furosemide, hydrochlorothiazide) or trovafloxacin because their effectiveness may be decreased by Embeda Extended-Release Capsules

This may not be a complete list of all interactions that may occur. Ask your health care provider if Embeda Extended-Release Capsules may interact with other medicines that you take. Check with your health care provider before you start, stop, or change the dose of any medicine.

How to use Embeda Extended-Release Capsules:

Use Embeda Extended-Release Capsules as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Embeda Extended-Release Capsules comes with an extra patient information sheet called a Medication Guide. Read it carefully. Read it again each time you get Embeda Extended-Release Capsules refilled.


• Take Embeda Extended-Release Capsules by mouth with or without food.


• Swallow Embeda Extended-Release Capsules whole. Do not dissolve, crush, or chew before swallowing.


• If you cannot swallow the capsule whole, contact your doctor. You may be able to open the capsule and sprinkle the pellets over a tablespoonful of applesauce. If you do this, swallow the applesauce and pellet mixture right away, followed by a glass of water. Do not crush or chew the medicine before swallowing. Do not store the mixture for future use. Dispose of the empty capsule as directed by your doctor or pharmacist.


• Take Embeda Extended-Release Capsules on a regular schedule to get the most benefit from it.


• Taking Embeda Extended-Release Capsules at the same time each day will help you remember to take it.


• Embeda Extended-Release Capsules should not be used more often than every 12 hours.


• Do not suddenly stop taking Embeda Extended-Release Capsules. If you need to stop taking Embeda Extended-Release Capsules, your dose may need to be slowly lowered in order to avoid withdrawal symptoms. Discuss any questions or concerns with your doctor.


• If you miss a dose of Embeda Extended-Release Capsules, take it as soon as possible. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once.

Ask your health care provider any questions you may have about how to use Embeda Extended-Release Capsules.

Important safety information:

• Embeda Extended-Release Capsules may cause dizziness or drowsiness. These effects may be worse if you take it with alcohol or certain medicines. Use Embeda Extended-Release Capsules with caution. Do not drive or perform other possibly unsafe tasks until you know how you react to it.


• Check with your doctor before you use medicines that may cause drowsiness (eg, sleep aids, muscle relaxers) while you are using Embeda Extended-Release Capsules; it may add to their effects. Ask your pharmacist if you have questions about which medicines may cause drowsiness.


• Do not drink alcohol or take any prescription or nonprescription medicines that have alcohol in them while you are taking Embeda Extended-Release Capsules. Ask your pharmacist if you have questions about whether any of your medicines have alcohol in them.


• Embeda Extended-Release Capsules may cause dizziness, lightheadedness, or fainting; alcohol, hot weather, exercise, or fever may increase these effects. To prevent them, sit up or stand slowly, especially in the morning. Sit or lie down at the first sign of any of these effects.


• Constipation is a common side effect of Embeda Extended-Release Capsules. Talk to your doctor about using laxatives or stool softeners to prevent or treat constipation while you use Embeda Extended-Release Capsules.


• Do not take more than the recommended dose or use more often than prescribed without checking with your doctor. If Embeda Extended-Release Capsules stops working well, contact your doctor.


• Tell your doctor or dentist that you take Embeda Extended-Release Capsules before you receive any medical or dental care, emergency care, or surgery.


• If you no longer need Embeda Extended-Release Capsules, check with your doctor or pharmacist about how to properly dispose of unused capsules.


• Use Embeda Extended-Release Capsules with caution in the ELDERLY; they may be more sensitive to its effects.


• Embeda Extended-Release Capsules should be used with extreme caution in CHILDREN younger than 18 years old; safety and effectiveness in children have not been confirmed.


• PREGNANCY and BREAST-FEEDING: If you become pregnant, contact your doctor. You will need to discuss the benefits and risks of using Embeda Extended-Release Capsules while you are pregnant. Embeda Extended-Release Capsules are found in breast milk. Do not breast-feed while taking Embeda Extended-Release Capsules.

When used for long periods of time or at high doses, Embeda Extended-Release Capsules may not work as well and may require higher doses to obtain the same effect as when originally taken. This is known as TOLERANCE. Talk with your doctor if Embeda Extended-Release Capsules stops working well. Do not take more than prescribed.

Some people who use Embeda Extended-Release Capsules for a long time may develop a need to continue taking it. People who take high doses are also at risk. This is known as DEPENDENCE or addiction. If you stop taking Embeda Extended-Release Capsules suddenly, you may have WITHDRAWAL symptoms. These may include anxiety; diarrhea; fever, runny nose, or sneezing; goose bumps and abnormal skin sensations; nausea; vomiting; pain; rigid muscles; rapid heartbeat; seeing, hearing, or feeling things that are not there; shivering or tremors; sweating; and trouble sleeping.

Possible side effects of Embeda Extended-Release Capsules:

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome:

Constipation; dizziness; drowsiness; dry mouth; headache; increased sweating; lightheadedness; mild itching; nausea; tiredness; vomiting.

Seek medical attention right away if any of these SEVERE side effects occur:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); chest pain; confusion; fainting; hallucinations; mental or mood changes; numbness of an arm or leg; pounding in the chest; seizures; severe dizziness or drowsiness; shortness of breath; slow, shallow breathing; sudden, severe nausea, vomiting, or headache.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

See also: Embeda side effects (in more detail)

If OVERDOSE is suspected:

Contact 1-800-222-1222 (the American Association of Poison Control Centers), your local poison control center, or emergency room immediately. Symptoms may include cold and clammy skin; convulsions; deep sleep; lightheadedness; limp muscles; loss of consciousness; low body temperature; pinpoint pupils; severe dizziness or drowsiness; shortness of breath; slow, shallow breathing; slowed heartbeat; wide pupils.

Proper storage of Embeda Extended-Release Capsules:

Store Embeda Extended-Release Capsules at 77 degrees F (25 degrees C). Brief storage at temperatures between 59 and 86 degrees F (15 and 30 degrees C) is permitted. Store away from heat, moisture, and light. Do not store in the bathroom. Keep Embeda Extended-Release Capsules out of the reach of children and away from pets

General information:

• If you have any questions about Embeda Extended-Release Capsules, please talk with your doctor, pharmacist, or other health care provider.


• Embeda Extended-Release Capsules are to be used only by the patient for whom it is prescribed. Do not share it with other people.


• If your symptoms do not improve or if they become worse, check with your doctor.


• Check with your pharmacist about how to dispose of unused medicine.

This information is a summary only. It does not contain all information about Embeda Extended-Release Capsules. If you have questions about the medicine you are taking or would like more information, check with your doctor, pharmacist, or other health care provider.

Issue Date: February 1, 2012

Database Edition 12.1.1.002

Copyright © 2012 Wolters Kluwer Health, Inc.

More Embeda resources

• Embeda Side Effects (in more detail)
• Embeda Dosage
• Embeda Use in Pregnancy & Breastfeeding
• Embeda Drug Interactions
• Embeda Support Group
• 15 Reviews for Embeda - Add your own review/rating

Compare Embeda with other medications

• Pain

Zomig

Generic Name: Zolmitriptan
Class: Selective Serotonin Agonists
VA Class: CN105
Chemical Name: (S)-4-[[3-[2-(dimethylamino)ethyl]indol-5-yl]methyl]-2-oxazolidinone
Molecular Formula: C₁₆H₂₁N₃O₂
CAS Number: 139264-17-8

Introduction

Selective serotonin (5-hydroxytryptamine; 5-HT) type 1B and 1D receptor agonist (“triptan”).^{1 2 3 4 5 6 7 8 9 10 11 14 15 21 22 23 24 27}

Uses for Zomig

Vascular Headaches

Acute treatment of migraine attacks with or without aura.^{1 27}

Not recommended for management of hemiplegic or basilar migraine or for prophylaxis of migraine.^{1 27}

Safety and efficacy not established for management of cluster headaches.^{1 27}

Zomig Dosage and Administration

Administration

Administer orally or intranasally.^{1 27 28}

Oral Administration

Administer orally as conventional or orally disintegrating tablets without regard to meals.¹

To achieve a dose <2.5 mg, manually break the scored 2.5-mg conventional tablet in half.¹ Do not break orally disintegrating tablets.¹

Just prior to administration of orally disintegrating tablet, remove tablet from blister package; peel open blister package, place tablet on tongue to dissolve, and swallow with saliva.¹

Administration of orally disintegrating tablet with liquid is not necessary.¹

Intranasal Administration

Administer intranasally as a single spray into 1 nostril.²⁸

Do not spray contents into eyes.²⁸

To administer, blow nose gently and remove protective cap just before use.²⁸ Hold nasal spray device gently and do not press plunger until tip is placed into nostril.²⁸ Block one nostril by pressing firmly on side of nose and put tip into other nostril as far as feels comfortable.²⁸ Tilt head slightly back and breathe gently through nose while pressing plunger firmly with thumb; a click may be heard.²⁸ Keep head tilted slightly back and remove tip of device from nose; breathe gently through mouth for 5–10 seconds.²⁸ Liquid may be felt in nose or back of throat.²⁸ Consult manufacturer’s patient information for complete directions.²⁸

Single-use spray pump; discard after use.²⁷

Dosage

Due to similarity in systemic exposure, dosage adjustments with oral and intranasal formulations should be similar; doses <5 mg can be achieved only through use of oral formulations.²⁷

Adults

Vascular Headaches

Migraine

Oral

Initially, ≤2.5 mg.¹ In clinical studies, single oral doses of 1 (not commercially available in US), 2.5, or 5 mg were effective, but the 2.5- and 5-mg doses were effective in a greater proportion of patients.¹ The 5-mg dose appears to offer little additional benefit and is associated with increased risk of adverse effects.¹

If headache recurs, dose may be repeated after ≥2 hours.¹

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.¹

Intranasal

5 mg (1 spray) as a single dose; individualize selection of dosage and administration route.²⁷

If headache recurs, dose may be repeated after 2 hours.²⁷

Following failure to respond to first dose, reconsider diagnosis of migraine prior to administration of a second dose.²⁷

Prescribing Limits

Adults

Vascular Headaches

Migraine

Oral

Maximum 10 mg in any 24-hour period.¹

Safety of treating an average of >3 headaches per 30-day period has not been established.¹

Intranasal

Maximum 10 mg in any 24-hour period.²⁷

Safety of treating an average of >4 headaches per 30-day period has not been established.²⁷

Special Populations

Hepatic Impairment

Generally use <2.5 mg as a single oral dose in patients with moderate to severe hepatic impairment; concurrent BP monitoring recommended.¹

Recommended doses can be achieved only with oral formulations; use of intranasal formulation not recommended.²⁷

Cautions for Zomig

Contraindications

• 
  

  Known or suspected ischemic heart disease (e.g., angina pectoris, history of MI, documented silent ischemia).^{1 27}

  
  


• 
  

  Coronary artery vasospasm (e.g., Prinzmetal variant angina).^{1 27}

  
  


• 
  

  Other serious underlying cardiovascular disease (e.g., uncontrolled hypertension).^{1 27}

  
  


• 
  

  Cerebrovascular syndromes (e.g., stroke syndromes, TIAs).²⁷

  
  


• 
  

  Hemiplegic or basilar migraine.^{1 27}

  
  


• 
  

  Treatment within previous 24 hours with another 5-HT₁ receptor agonist or an ergot alkaloid.^{1 27} (See Specific Drugs under Interactions.)

  
  


• 
  

  Concurrent or recent (within 2 weeks) treatment with an MAO-A inhibitor.^{1 27} (See Specific Drugs under Interactions.)

  
  


• 
  

  Known sensitivity to zolmitriptan or any ingredient in the formulation.^{1 27}

  
  

Warnings/Precautions

Warnings

Use only in patients in whom a clear diagnosis of migraine has been established.^{1 27}

Cardiac Effects

Risk of coronary vasospasm, myocardial ischemia and/or infarction, life-threatening cardiac rhythm disturbances, and death with use of 5-HT₁ receptor agonists.^{1 27}

Use not recommended in patients with symptomatic Wolff-Parkinson-White syndrome or cardiac arrhythmias associated with other accessory pathway conduction disorders.^{1 27}

Use not recommended in patients with known or suspected ischemic or vasospastic heart disease or in patients in whom unrecognized CAD is likely (e.g., postmenopausal women; men >40 years of age; patients with risk factors such as hypertension, hypercholesterolemia, smoking, obesity, diabetes, or family history of CAD) unless there is satisfactory evidence from prior cardiovascular evaluation that patient does not have CAD, ischemic heart disease, or other underlying cardiovascular disease.^{1 27}

Administer initial dose to patients with risk factors for CAD who have completed satisfactory cardiovascular evaluation under medical supervision (e.g., in clinician's office, possibly followed by ECG) unless patient previously received the drug.^{1 27}

Periodic cardiovascular evaluation recommended in patients with risk factors for CAD if receiving intermittent long-term therapy.^{1 27}

Patients with symptoms suggestive of angina after receiving zolmitriptan should be evaluated for the presence of CAD or predisposition to Prinzmetal variant angina before receiving additional doses.^{1 27}

Cerebrovascular Events

Possible cerebral or subarachnoid hemorrhage, stroke, and other cerebrovascular events, sometimes fatal, with use of 5-HT₁ receptor agonists.^{1 27}

Risk of certain cerebrovascular events (e.g., stroke, hemorrhage, TIA) may be increased in patients with migraine.^{1 27}

Other Cardiovascular or Vasospastic Effects

Peripheral vascular ischemia and colonic ischemia with abdominal pain and bloody diarrhea reported with use of 5-HT₁ receptor agonists.^{1 27} Further evaluation recommended if signs or symptoms of decreased arterial flow (e.g., ischemic bowel syndrome, Raynaud's syndrome) occur following administration.^{1 27}

Substantial increases in BP, including hypertensive crises, reported rarely with 5-HT₁ receptor agonists in patients with or without history of hypertension.^{1 27}

Increases in mean pulmonary artery pressure observed following administration of a 5-HT₁ receptor agonist to patients with suspected CAD who were undergoing cardiac catheterization.^{1 27}

Serotonin Syndrome

Potentially life-threatening serotonin syndrome reported during concurrent therapy with 5-HT₁ receptor agonists (“triptans”) and SSRIs or selective serotonin- and norepinephrine-reuptake inhibitors (SNRIs).^{27 29} Symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile BP, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination), and/or GI symptoms (e.g., nausea, vomiting, diarrhea).^{27 29}

Local Effects

Possible local irritation or soreness after intranasal administration.²⁷ Adverse effects perceived in nasopharynx, occasionally severe, usually resolve within 1 hour.²⁷

No clinically important nasopharyngeal changes observed by examination following repeated use for up to 1 year’s duration.²⁷

General Precautions

Ocular Effects

Possible accumulation of zolmitriptan and/or its metabolites in melanin-rich tissues (e.g., eye) over time, resulting in potential toxicity in these tissues with extended use.^{1 27}

Phenylketonuria

Each 2.5- or 5-mg Zomig-ZMT orally disintegrating tablet contains aspartame, which is metabolized in GI tract to provide 2.81 or 5.62 mg of phenylalanine, respectively.¹ Conventional tablets do not contain aspartame.¹

Specific Populations

Pregnancy

Category C.^{1 27}

Lactation

Distributed into milk in rats; not known whether distributed into human milk.^{1 27} Caution advised if zolmitriptan is used.^{1 27}

Pediatric Use

Safety and efficacy not established in children <18 years of age; use not recommended.^{1 27}

Geriatric Use

Pharmacokinetic profile similar to that in younger adults.^{1 27} However, patients >65 years of age were excluded from clinical studies; safety and efficacy not established.^{1 27}

Hepatic Impairment

Substantial elevation of BP observed in some patients with moderate-to-severe hepatic impairment following 10-mg oral dose.^{1 27} Use with caution in patients with hepatic impairment;^{1 27} BP monitoring and dosage adjustment recommended.^{1 27}

Common Adverse Effects

Dizziness,^{1 27} paresthesia,^{1 27} hyperesthesia,^{1 27} neck/throat/jaw/chest symptoms (e.g., pain, tightness, pressure, heaviness),^{1 27} nausea,^{1 27} somnolence,^{1 27} warm or cold sensation,¹ asthenia,^{1 27} dry mouth,^{1 27} dyspepsia¹ ; with intranasal therapy, also nasal cavity disorder/discomfort,²⁷ unusual taste.²⁷

Interactions for Zomig

Appears to be metabolized by CYP1A2; active N-desmethyl metabolite appears to be further metabolized by MAO-A.^{22 23 24 26}

Specific Drugs

Drug	Interaction	Comments
Acetaminophen	Increased time to peak plasma acetaminophen concentrations1 27
Antidepressants, SSRIs (e.g., citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, sertraline) and SNRIs (e.g., duloxetine, venlafaxine)	Potentially life-threatening serotonin syndrome27 29 Zolmitriptan pharmacokinetics or effect on BP not altered by fluoxetine pretreatment1 27 30	Observe carefully if used concomitantly, particularly during treatment initiation, dosage increases, or when another serotonergic agent is initiated27 29
Cimetidine	Increased half-life and systemic exposure to zolmitriptan and its active metabolite1 27
Ergot alkaloids (e.g., ergotamine, dihydroergotamine, methysergide)	Additive vasospastic effects1 27	Use within 24 hours contraindicated1 27
5-HT1 receptor agonists	Additive vasospastic effects1 27	Use within 24 hours contraindicated1 27
MAO inhibitors	Increased plasma concentrations of zolmitriptan and its active metabolite with concurrent use of MAO-A inhibitors; 1 27 selegiline (selective MAO-B inhibitor) did not affect pharmacokinetics of zolmitriptan or its active metabolite27	Use of oral or intranasal zolmitriptan within 2 weeks of MAO-A inhibitor contraindicated1 27
Metoclopramide	Metoclopramide (single 10-mg dose) did not affect pharmacokinetics of zolmitriptan or its metabolites1 27
Oral contraceptives	Increased plasma zolmitriptan concentrations1 27
Propranolol	Increased plasma zolmitriptan concentrations; peak zolmitriptan concentration may be delayed1 27
Xylometazoline	Topical application of xylometazoline to nasal mucosa 30 minutes prior to intranasal zolmitriptan did not affect zolmitriptan pharmacokinetics27

Zomig Pharmacokinetics

Absorption

Bioavailability

Well absorbed after oral administration, with peak plasma concentrations attained within 1.5 hours (conventional tablets) or 3 hours (orally disintegrating tablets).¹ Rapidly absorbed via the nasopharynx after intranasal administration, with peak plasma concentrations attained within 3 hours.²⁷

Mean absolute bioavailability after oral administration is approximately 40%;¹ mean bioavailability of nasal solution is 102% compared with oral tablet.²⁷

Mean plasma concentrations after oral administration are increased by up to 1.5-fold in females compared with males.^{1 27}

Food

Food does not substantially affect bioavailability.^{1 27}

Distribution

Plasma Protein Binding

25%.^{1 27}

Elimination

Metabolism

Undergoes hepatic metabolism to form 3 principal metabolites, including N-desmethyl zolmitriptan (5-HT_1B/1D potency is 2–6 times that of zolmitriptan).^{1 22 23 24 27} Formation of N-desmethyl zolmitriptan may depend on CYP1A2; MAO-A appears to mediate metabolism of N-desmethyl zolmitriptan.^{22 23 24 26}

Elimination Route

Excreted in urine (65%) and feces (30%) as unchanged drug and metabolites;^{1 24} dose recovered in urine as unchanged drug (8%) and indole acetic acid (31%), N-oxide (7%), and N-desmethyl (4%) metabolites.¹

Half-life

Approximately 3 hours for zolmitriptan and active N-desmethyl metabolite after oral or intranasal administration.^{1 13 23 24 27}

Special Populations

In patients with severe hepatic impairment, peak plasma concentrations, time to achieve peak plasma concentrations, and AUC are 1.5-, 2-, and 3-fold higher, respectively, than in healthy individuals after oral administration.^{1 27} Pharmacokinetics of nasal spray not evaluated in patients with hepatic impairment.²⁷

In patients with severe renal impairment (Cl_cr 5–25 mL/minute), clearance is reduced by 25% after oral administration; no substantial change in clearance in patients with moderate renal impairment (Cl_cr 26–50 mL/minute).¹ Pharmacokinetics of nasal spray not evaluated in patients with renal impairment.²⁷

Stability

Storage

Oral

Conventional and Orally Disintegrating Tablets

20–25°C; protect from light and moisture.¹

Intranasal

Solution

20–25°C.²⁷

ActionsActions

• 
  

  Binds with high affinity to 5-HT_1B and 5-HT_1D receptors.^{1 2 3 4 5 6 7 8 9 10 11 14 15 21 22 23 24 27}

  
  


• 
  

  Structurally and pharmacologically related to other selective 5-HT_1B/1D receptor agonists (e.g., almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan, sumatriptan).^{21 22}

  
  


• 
  

  Precise mechanism of action not established; may ameliorate migraine through selective constriction of certain intracranial blood vessels, inhibition of neuropeptide release, and reduced transmission in trigeminal pain pathway.^{1 21 22 23 27}

  
  

Advice to Patients

• 
  

  Importance of immediately informing clinician of occurrence of tightness, pain, pressure, or heaviness in chest, throat, jaw, or neck; sudden or severe abdominal pain; shortness of breath or wheezing; heart throbbing; facial swelling (e.g., eyelids, face, lips); tongue, mouth or throat swelling; rash or hives and of not taking zolmitriptan again until evaluated by a clinician.^{1 27} Importance of informing clinician of any other symptoms not understood by patient.^{1 27}

  
  


• 
  

  Importance of adhering to prescribed directions for use.^{1 27 28} Importance of patient reading manufacturer's patient information before initial use and each time prescription is refilled.^{1 28}

  
  


• 
  

  For patients taking zolmitriptan orally disintegrating tablets, importance of not removing tablet from blister package until just before administering dose;¹ importance of peeling blister open and placing tablet on tongue to dissolve and be swallowed with saliva.¹

  
  


• 
  

  Importance of informing patients with phenylketonuria that orally disintegrating tablets contain aspartame.¹

  
  


• 
  

  Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, dietary supplements, and herbal supplements, as well as any concomitant illnesses (e.g., cardiovascular disease).^{1 27}

  
  


• 
  

  Importance of informing patients of risk of serotonin syndrome with concurrent use of zolmitriptan and an SSRI or SNRI.^{27 29} Importance of seeking immediate medical attention if symptoms of serotonin syndrome develop.^{27 29}

  
  


• 
  

  Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.^{1 27}

  
  


• 
  

  Importance of informing patients of other important precautionary information.^{1 27} (See Cautions.)

  
  

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Zolmitriptan

Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Nasal	Solution	5 mg/0.1 mL	Zomig Nasal Spray	AstraZeneca
Oral	Tablets, film-coated	2.5 mg	Zomig	AstraZeneca
		5 mg	Zomig	AstraZeneca
	Tablets, orally disintegrating	2.5 mg	Zomig-ZMT (with aspartame)	AstraZeneca
		5 mg	Zomig-ZMT (with aspartame)	AstraZeneca

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 03/2011. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Zomig 2.5MG Tablets (ASTRAZENECA): 6/$156 or 18/$441.97

Zomig 5MG Solution (ASTRAZENECA): 6/$216 or 18/$615.99

Zomig 5MG Tablets (ASTRAZENECA): 3/$95.99 or 9/$259.96

Zomig ZMT 2.5MG Dispersible Tablets (ASTRAZENECA): 6/$155.99 or 18/$452.99

Zomig ZMT 5MG Dispersible Tablets (ASTRAZENECA): 3/$85.99 or 9/$230.98

Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.

The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. AstraZeneca Pharmaceuticals LP. Zomig (zolmitriptan) tablets and Zomig-ZMT(zolmitriptan) orally disintegrating tablets prescribing information. Wilmington, DE; 2005 May.

2. Visser WH, Klein KB, Cox RC et al. 311C90, a new central and peripherally acting 5-HT1D receptor agonist in the acute oral treatment of migraine: a double-blind, placebo-controlled, dose-range finding study. Neurology. 1996; 46:522-6.

3. Dahlof C, Diener HC, Goadsby PJ et al. Zolmitriptan, a 5-HT1B/1D receptor agonist for the acute oral treatment of migraine: a multicentre, dose-range fnding study. Eur J Neurol 1998; 5:535-43. [PubMed 10210888]

4. Rapoport AM, Ramadan NM, Adelman JU et al. Optimizing the dose of zolmitriptan (Zomig, 311C90) for the acute treatment of migraine. A multicenter, double-blind, placebo-controlled, dose range-finding study. Neurology. 1997; 49:1210-8. [IDIS 397204] [PubMed 9371896]

5. Solomon GD, Cady RK, Klapper JA et al. Clinical efficacy and tolerability of 2.5 mg zolmitriptan for the acute treatment of migraine. Neurology. 1997; 49:1219-25. [IDIS 397205] [PubMed 9371897]

6. Dowson AJ, MacGregor EA, Purdy RA et al. Zolmitriptan orally disintegrating tablet is effective in the acute treatment of migraine. Cephalalgia. 2002; 22:101-6. [PubMed 11972576]

7. The International 311C90 Long-term Study Group. The long-term tolerability and efficacy of oral zolmitriptan (Zomig, 311C90) in the acute treatment of migraine. An international study. Headache. 1998; 38:173-83. [PubMed 9563207]

8. Tepper SJ, Donnan GA, Dowson AJ et al. A long-term study to maximize migraine relief with zolmitriptan. Curr Med Res Opin. 1999; 15:254-71. [PubMed 10640258]

9. Tuchman M, Edvinsson L, Geraud G et al. Zolmitriptan provides consistent migraine relief when used in the long-term. Curr Med Res Opin. 1999; 15:272-81. [PubMed 10640259]

10. Gallagher RM, Dennish G, Spierings ELH et al. A comparative trial of zolmitriptan and sumatriptan for the acute oral treatment of migraine. Headache. 2000; 40:119-28. [PubMed 10759911]

11. Gruffyd-Jones K, Kies B, Middleton A et al. Zolmitriptan versus sumatriptan for the acute oral treatment of migraine: a randomized, double-blind, international study. Eur J Neurol. 2001; 8:237-45.

12. Oldman AD, Smith LA, McQuay HJ et al. Pharmacological treatment for acute migraine: quantitative systematic review. Pain. 2002; 97:247-57.

13. Ferrari MD, Goadsby PJ, Roon KI et al. Triptans (serotonin, 5-HT1B/1D agonists) in migraine: detailed results and methods of a meta-analysis of 53 trials. Cephalalgia. 2002; 22:633-58. [PubMed 12383060]

14. Matchar DB, Young WB, Rosenberg JH et al. Evidence-based guidelines for migraine headache in the primary care setting: pharmacological management of acute attacks. From American Academy of Neurology web site ().

15. Silberstein SD, for the US Headache Consortium. Practice parameter: evidence-based guidelines for migraine headache (an evidence-based review): report of the quality standards subcommittee of the American Academy of Neurology. Neurology. 2000; 55:754-63. [IDIS 453389] [PubMed 10993991]

16. American Medical Association Council on Scientific Affairs. Aspartame: review of safety issues. JAMA. 1985; 254:400-2. [IDIS 202002] [PubMed 2861297]

17. Gossel TA. A review of aspartame: characteristics, safety and uses. US Pharm. 1984; 9:26,28-30.

18. Food and Drug Administration. Aspartame as an inactive ingredient in human drug products; labeling requirements. Proposed rule. [21 CFR Part 201] Fed Regist. 1983; 48:54993-5.

19. Food and Drug Administration. Food additives permitted for direct addition to food for human consumption; aspartame. Final rule. [21 CFR Part 172] Fed Regist. 1983; 48:31376-82.

20. Anon. Aspartame and other sweeteners. Med Lett Drugs Ther. 1982; 24:1-2.

21. Tfelt-Hansen P, De Vries P, Saxena PR. Triptans in migraine. A comparative review of pharmacology, pharmacokinetics, and efficacy. Drugs. 2000; 60:1259-87.

22. Deleu D, Hanssens Y. Current and emerging second-generation triptans in acute migraine therapy: a comparative review. J Clin Pharmacol. 2000; 40:687-700. [IDIS 449430] [PubMed 10883409]

23. Dowson AJ, Charlesworth B. Review of zolmitriptan and its clinical applications in migraine. Expert Opin Pharmacother. 2002; 3:993-1005. [PubMed 12083998]

24. Spencer CM, Gunasekara NS, Hills C. Zolmitriptan. A review of its use in migraine. Drugs. 1999; 58:347-74. [PubMed 10473025]

25. GlaxoSmithKline. Amerge (naratriptan hydrochloride) tablets prescribing information. Research Triangle Park, NC; 2002 Oct.

26. AstraZeneca, Wilmington, DE: Personal communication.

27. AstraZeneca. Zomig (zolmitriptan) nasal spray prescribing information. Wilmington, DE; 2006 July.

28. AstraZeneca. Zomig (zolmitriptan) nasal spray patient summary of information. Wilmington, DE; 2005 Jun.

29. Food and Drug Administration. Public health advisory: combined use of 5-hydroxytryptamine receptor agonists (triptans), selective serotonin reuptake inhibitors (SSRIs) or selective serotonin/norepinephirne reuptake inhibitors (SNRIs) may result in life-threatening serotonin syndrome. Rockville, MD; 2006 Jul 19. From the FDA website: (, , and ).

30. Smith DA, Cleary EW, Watkins S et al. Zolmitriptan (311C90) does not interact with fluoxetine in healthy volunteers. Int J Clin Pharmacol Ther. 1998; 36:301-5. [PubMed 9660035]

More Zomig resources

• Zomig Side Effects (in more detail)
• Zomig Use in Pregnancy & Breastfeeding
• Drug Images
• Zomig Drug Interactions
• Zomig Support Group
• 23 Reviews for Zomig - Add your own review/rating

• Zomig Prescribing Information (FDA)


• Zomig Consumer Overview


• Zomig Advanced Consumer (Micromedex) - Includes Dosage Information


• Zomig MedFacts Consumer Leaflet (Wolters Kluwer)


• Zolmitriptan Professional Patient Advice (Wolters Kluwer)

Compare Zomig with other medications

• Cluster Headaches
• Cyclic Vomiting Syndrome
• Migraine

Hepatect CP

HEPATECT CP 50 IU/ml solution for infusion

Human hepatitis B immunoglobulin for intravenous administration

Information for medical or health care professionals is provided at the end of this leaflet in a separate section.

Read all of this leaflet carefully before you start using this medicine

• Keep this leaflet. You may want to read it again.


• If you have any further questions, ask your doctor or pharmacist.


• This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.


• If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet:

1. What HEPATECT CP is and what it is used for

2. Before you use HEPATECT CP

3. How to use HEPATECT CP

4. Possible side-effects

5. How to store HEPATECT CP

6. Further information

What Hepatect Cp Is And What It Is Used For

HEPATECT CP contains the active ingredient human hepatitis B immunoglobulin, which can protect you from hepatitis B. Hepatitis B is an inflammation of the liver caused by the hepatitis B virus.

HEPATECT CP is a solution for infusion (into a vein) and comes in vials containing 2 ml (100 International Units [IU]), 10 ml (500 IU) and 40 ml (2000 IU).

HEPATECT CP is used to give immediate and long-term immunity (protection) to:

• prevent hepatitis B infection in patients who have not been vaccinated or fully vaccinated against hepatitis B and who are at risk of infection with hepatitis B.


• prevent infection of a transplanted liver in patients who test positive for hepatitis B.


• newborn babies whose mothers are infected with the hepatitis B virus.


• protect patients for whom hepatitis B vaccination has not provided adequate protection.

Before You Use Hepatect Cp

You should not be given HEPATECT CP if you,

• are allergic (hypersensitive) to human immunoglobulin or any of the other ingredients of HEPATECT CP (see list of ingredients in Section 6). An allergic reaction may include rash, itching, difficulty breathing or swelling of the face, lips, throat or tongue.


• have already been fully vaccinated against hepatitis B and you are immune.

Take special care with HEPATECT CP (and talk to your doctor) if you

• suffer from a condition with low antibody levels in your blood (hypo- or agammaglobulinemia)


• have had a reaction to other antibodies (in rare cases you may be at risk of allergic reactions)

Your doctor will take special care if you are overweight, elderly, diabetic, or if you suffer from high blood pressure, low blood volume (hypovolaemia), have an IgA deficiency, have problems with your blood vessels (vascular diseases) or are at risk for thrombotic events.

Inform your doctor if you have been vaccinated against hepatitis B within the past four weeks. You may need to be re-vaccinated if you are given HEPATECT CP.

Please note - reactions

You will be carefully observed during the infusion period with HEPATECT CP to make sure that you do not suffer a reaction. Your doctor will make sure that the rate at which HEPATECT CP is infused is suitable for you.

If you have a reaction during the infusion of HEPATECT CP, tell your doctor immediately. The rate of infusion can be slowed or the infusion can be stopped altogether.

Information on transmission of infectious agents

HEPATECT CP is made from human plasma (the liquid part of blood). When medicines are made from human blood or plasma, it is important to prevent infections being passed on to patients. Blood donors are tested for viruses and infections. Manufacturers of these products also process the blood or plasma to inactivate or remove viruses. Despite these measures, when medicines prepared from human blood or plasma are given, the possibility of passing on infection cannot be totally excluded.

Taking other medicines

Please tell your doctor if you are taking or have recently taken any other medicines including medicines obtained without a prescription.

HEPATECT CP can reduce the effectiveness of some vaccines such as:

• measles


• rubella


• mumps


• chicken pox

You may have to wait up to 3 months before you can have some vaccines.

Effects on blood tests

HEPATECT CP can affect blood tests. If you have a blood test after receiving HEPATECT CP, please inform the person taking your blood or your doctor that you have received HEPATECT CP.

Pregnancy and breast-feeding

Ask your doctor for advice before taking any medicine.

Your doctor will decide if HEPATECT CP may be used during pregnancy and breast-feeding.

Driving and using machines

HEPATECT CP has no known effects on your ability to drive or use machines.

How To Use Hepatect Cp

HEPATECT CP is intended for intravenous administration (infusion into a vein). It is given to you by a doctor or nurse. The dose will depend on your condition and your body weight. Your doctor will know the right amount to give you.

At the beginning of your infusion you will receive HEPATECT CP at a slow rate. Your doctor may then gradually increase the infusion rate.

If you have any further questions on the use of this product, ask your doctor or nurse.

Hepatect CP Side Effects

Like all medicines, HEPATECT CP can have side effects, although not everybody gets them.

Rarely, the following may occur:

• chills


• headache


• fever


• vomiting


• malaise (feeling sick)


• nausea (urge to vomit)


• low blood pressure


• allergic reactions


• skin (cutaneous) reactions such as erythema (redness), itching


• tachycardia (faster heart beat)

Very rarely, the following may occur:

• severe allergic reactions (anaphylactic shock)


• joint pain

With human immunoglobulin the following has been observed:

• temporary meningitis (inflammation of the brain lining)


• decrease of red blood cells (reversible haemolytic anaemia/haemolysis)


• an increase in the serum creatinine (a waste product) and/or sudden kidney failure


• cases of blood clots in the veins (thromboembolic reactions) have been reported in the elderly, in patients with signs of cerebral or cardiac ischemia, and in overweight and patients with very low blood volume (severely hypovolaemic).

If a side effect occurs, the infusion rate will be decreased or stopped.

If any of the side effects gets serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

How To Store Hepatect Cp

Keep out of the reach and sight of children.

Your pharmacist or doctor knows how to store HEPATECT CP.

It should be kept in the outer carton to protect it from light.

HEPATECT CP should be stored in a refrigerator at 2-8 °C. Do not freeze.

Further Information

What HEPATECT CP contains:

• The active substance of HEPATECT CP is human hepatitis B immunoglobulin for intravenous administration.
  
  HEPATECT CP contains 50 mg/ml of human plasma protein of which at least 96 % is immunoglobulin G (IgG). The content of hepatitis B antibody is 50 IU/ml. The maximum immunoglobulin A (IgA) content is 2 mg/ml. The IgG subclass distribution is approx.
  
  59 % IgG1, 35 % IgG2, 3 % IgG3 and 3 % IgG4.


• The other ingredients are glycine and water for injections.

What HEPATECT CP looks like and the contents of the pack

HEPATECT CP is a solution for infusion. The solution is clear to faintly opalescent (milky colours like an opal) and colourless to pale yellow.

Pack containing 1 vial with 100 IU in 2 ml solution

Pack containing 1 vial with 500 IU in 10 ml solution

Pack containing 1 vial with 2000 IU in 40 ml solution

Marketing Authorisation Holder and Manufacturer:

Biotest Pharma GmbH

Landsteinerstrasse 5

63303 Dreieich

Germany

Tel.:+ 49 6103 801-0

Fax:+ 49 6103 801-150 and -727

e-mail:info@biotest.de

For any information about this medicine, please contact the local representative of the Marketing Authorisation Holder:

Biotest (UK) Ltd.

28 Monkspath Business Park

Highlands Road

Shirley

Solihull

West Midlands

B90 4NZ

Tel:+44 (0)121 733 3393

Fax:+44(0)121 733 3066

e-mail:biotestuk@biotestuk.com

PL 04500/0006

This leaflet was last approved in October 2008.